A living organism generally does not display immune response to a self-composing antigen. This is called natural or innate immunological tolerance. On the other hand, even if an antigen is originally heterogeneous to a living organism, it may not react to the immune response which is displayed on dosing of the antigen, depending on when it is dosed (especially at viviparous period and neonatal period), how it is dosed (for example using immunosuppressant), and in what form it is dosed (e.g. a denatured substance is removed before dosing protein antigen). This is called acquired tolerance. Immune response is generally thought as celullar or humoral response to a non-self on having distinguished self from others (non-self). Self and non-self is distinguished by an antigen receptor located on the lymphocyte surface. When a substance is recognized as being non-self, lymphocytes proliferate to demonstrate cytotoxity or produce antibody to the substance. However, at the primary recognition stage by lymphocytes, a step is necessary in which a foreign substance (non-self) is incorporated into dendritic cells or macrophages, and is then presented in a way as to be recognized by T lymphocytes. Thus the self/non-self recognition is thought to occur at the interaction level of dendritic cells or macrophages, and T lymphocytes.
Meanwhile, gene therapy, in which a foreign gene, obtained from such as recombinant DNA experiments is transferred into a patient's somatic cell in order to treat the patient's gene disease, through the gene function, has now been applied to various gene diseases such as cancer, immunodeficiency, cardiovascular diseases, or the like. But what prevents gene therapy most from being brought in practice is the immune responsiveness to a component of a vector (a vehicle for gene transfer) used for gene transfer, as mentioned above. In other words, the technique of gene transfer into cells has almost been completed, but the problem remains in that a vector should be used anyway for gene transfer. The known gene transfer methods using a vector involve viral vector methods using various kinds of virus systems such as retrovirus, adenovirus, lentivirus and the like; liposome methods in which a membrane encompassing DNA is fused with the cell; microinjection methods wherein a gene is transferred directly into the cell; and a method using Sendai virus (HVJ) which shows high affinity with the cell, wherein the size of inserting DNA will not be restricted (J. Biol. Chem. 264, 12126-12129, 1989, J. Biol. Chem. 266, 3361-3364, 1991, Bioche. Biophys. Res. Commun. 186, 129-134, 1992, Circ. Res. 73, 898-905, 1993, Science 243, 375-378, 1989, J. Clin. Invest 94, 978-984, 1994).
In any of the above mentioned gene transfer techniques, a transfer vector is foreign to human body, thus immune response is caused to the vector component resulting in the rejection of the vector by the living body sooner or later (generally within two weeks to a month). In case of viral vector, for example, a vector component is expressed as a protein in the infected cell, which protein subsequently is expressed as a peptide on the cell surface. The vector-derived peptide is then recognized by T lymphocytes that consequently kill the infected cell so that the vector (virus) is rejected. Thus the present gene therapy has succeeded in gene transfer itself, but a defect still remains that a long-sustaining effect has not successfully been attained.
Further, there are methods of acquiring immunological tolerance such as a method inducing immunological tolerance to mammal animals by not making them intake a fat-soluble component or a substance including fat-soluble component simultaneously with the antigen (Japanese Laid-Open Patent Application No. 9-194393). Also a method is known which uses a pharmaceutical preparation having a medicament as its effective component which has no substantial pharmacological effect when orally dosed, meanwhile showing the effect when injected, which effect, however, diminishes when injected repeatedly. Said pharmaceutical preparation is composed of a preparation for oral dose including the medicament with enough dose/unit to induce oral immunological tolerance and a preparation for injection including the medicament that is to be administrated after the oral immunological tolerance has been induced (Japanese Laid-Open Patent Application No. 10-298101). Furthermore there is a method which uses an artificial organ in order to establish immunological tolerance in the recipient. Said artificial organ is prepared by removing an organ from an animal showing specific immunological tolerance to the recipient. Thus peripheral immune mechanism composed of lymphocytes or the like of the transplanted organ will not attack human histocompatibility complex when transplanted to the recipient, which results in good survival of the transplanted organ (Japanese Laid-Open Patent Application No. 9-187470).